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Biomedical subjects

F Miraldi

Publications and source records attributed to F Miraldi.

At least 37 records · Page 2Linked to original sources
PubMed1996

Attention and regional cerebral blood flow in posttraumatic stress disorder patients with substance abuse histories.

Performance on an attentional task was assessed in posttraumatic stress disorder patients with substance abuse histories (PTSD-SA). Positron emission tomography (PET) was used to measure concurrent regional cerebral blood flow (rCBF). Eight male PTSD-SA patients and eight normal subjects each received three serial PET scans with 15O-labeled water under the following conditions: (1) resting, (2) auditory continuous performance task (ACPT1), and (3) repeat auditory task (ACPT2). PTSD-SA patients made more errors of commission on the ACPT than normal subjects. Examination of right frontal and parietal cortex ACPT task substrates revealed decreased parietal blood flow in PTSD-SA, which may represent a pathophysiology for poor attentional task performance in PTSD-SA. Attentional problems may underlie other symptomatology in PTSD.

Adult↗
PubMed1996

PET measurement of neuroreceptor occupancy by typical and atypical neuroleptics.

UNLABELLED: The goal of this study was to use PET and 11C-N-methylspiperone (11C-NMSP) to measure the difference in relative occupancy of serotonin (5-hydroxytryptamine-2 or 5-HT2A) and dopamine-2 (D2) neuroreceptors in subjects being treated with typical or atypical antipsychotic drugs. METHODS: We used PET and single-dose 11C-NMSP to measure receptor indices and relative receptor occupancy of 5-HT2A receptors in frontal cortex and D2 receptors in basal ganglia in five subjects who were neuroleptic free, five subjects who were being treated with typical antipsychotic drugs and five subjects who were being treated with clozapine, an atypical antipsychotic drug. RESULTS: Among the three groups, there were significant differences in 5-HT2A indices, D2 indices and the ratio of 5-HT2A to D2 indices. With no overlap, the 5-HT2A index separated all subjects who received clozapine and the D2 index separated the remaining two groups. CONCLUSION: Typical antipsychotic and atypical antipsychotic subjects do have differing patterns of 5-HT2A and D2 relative receptor occupancy when measured with a single PET scan, single 11C-NMSP radiotracer dose and no separately injected "cold" pharmaceutical.

Adult↗
PubMed1995

Effects of a ketogenic diet on tumor metabolism and nutritional status in pediatric oncology patients: two case reports.

OBJECTIVE: Establish dietary-induced ketosis in pediatric oncology patients to determine if a ketogenic state would decrease glucose availability to certain tumors, thereby potentially impairing tumor metabolism without adversely affecting the patient's overall nutritional status. DESIGN: Case report. SETTING: University Hospitals of Cleveland. SUBJECTS: Two female pediatric patients with advanced stage malignant Astrocytoma tumors. INTERVENTIONS: Patients were followed as outpatients for 8 weeks. Ketosis was maintained by consuming a 60% medium chain triglyceride oil-based diet. MAIN OUTCOME MEASURES: Tumor glucose metabolism was assessed by Positron Emission Tomography (PET), comparing [Fluorine-18] 2-deoxy-2-fluoro-D-glucose (FDG) uptake at the tumor site before and following the trial period. RESULTS: Within 7 days of initiating the ketogenic diet, blood glucose levels declined to low-normal levels and blood ketones were elevated twenty to thirty fold. Results of PET scans indicated a 21.8% average decrease in glucose uptake at the tumor site in both subjects. One patient exhibited significant clinical improvements in mood and new skill development during the study. She continued the ketogenic diet for an additional twelve months, remaining free of disease progression. CONCLUSION: While this diet does not replace conventional antineoplastic treatments, these preliminary results suggest a potential for clinical application which merits further research.

Astrocytoma↗
PubMed1995

Effect of human chorionic gonadotropin before spermatic vessel ligation in the prepubertal rat testis.

After single stage Fowler-Stephens orchiopexy testicular atrophy is common. Previous experimental study in the scrotal testis of the adult rat has shown that ligation of the internal spermatic artery often causes focal testicular infarction or atrophy and exogenous human chorionic gonadotropin increases testicular blood flow. We questioned whether division of the internal spermatic artery in the undescended rat testis would also cause testicular injury and hypothesized that these changes might be prevented by administering human chorionic gonadotropin before vessel ligation. Two groups of 20-day-old Sprague-Dawley male rats were subjected to unilateral internal spermatic artery ligation. Group 1 (control) received no human chorionic gonadotropin, while group 2 received 10 IU human chorionic gonadotropin daily from days 3 to 17 of life. At 3 months testicular blood flow was quantitated using 141cerium radioactive microspheres. The results indicated that blood flow on the operated side was lower than on the nonoperated side but the change was not statistically significant. Human chorionic gonadotropin had no effect on blood flow to the operated testes. Gross testicular weights of operated versus nonoperated gonads were similar in rats that did and did not receive human chorionic gonadotropin. Pathological evaluation revealed normal histology in all testes. These results do not support the use of human chorionic gonadotropin preoperatively to stimulate collateral testicular blood flow.

Animals↗
PubMed1994

Specific beta-adrenergic receptor binding of carazolol measured with PET.

UNLABELLED: Carazolol is a promising high-affinity beta-adrenergic receptor ligand for the noninvasive determination of beta receptor status using PET. Earlier investigations demonstrated specific receptor binding of carazolol in mice. These PET studies with S(-)-[2"-11C]carazolol in pigs were performed to explore the utility of the tracer for PET receptor studies. METHODS: Tracer uptake in the heart and lung was measured by PET as a function of time. Receptors were blocked with propranolol and different doses of ICI 118,551 to estimate specific binding. Fluorine-18-1"-Fluorocarazolol and the less active R-enantiomer of [11C]-carazolol were also studied. RESULTS: Specific receptor binding was 75% of the total uptake in the heart, preventable and displaceable by propranolol. Dose-dependent competition showed that carazolol binds in vivo to beta 1 and to beta 2 subtypes. Uptake of the labeled R(+) enantiomer of carazolol was not receptor-specific. CONCLUSIONS: Carazolol labeled with 11C or 18F is a strong candidate for use in receptor estimation with PET. The in vivo observations were consistent with its known high affinity and slow receptor dissociation rate. Its high specific receptor uptake and low metabolism allow existing kinetic models to be applied for receptor measurements. The 11C label is convenient for repeated administrations, though 18F allowed the long observation periods necessary for measurement of the receptor dissociation rate. If needed, nonspecific uptake can be estimated without pharmacologic intervention by using the labeled R enantiomer.

Adrenergic beta-Antagonists↗
PubMed1993

[Immunostimulation in heart surgery: thymostimulin. Preliminary data].

The immunodepressive effect of surgical procedures is well known. Immunotherapy with thymic hormones has used a long time to prevent surgical immunitary damage. In cardiac surgery, we can observe a hard immunitary depression caused by the cardiopulmonary bypass (CBP). In this paper we evaluate the response to immunotherapy, with an extractive thymic hormone: thymostimulin at the dosage of 1 mg/kg/day; 20 patients of a group of 40 underwent CBP. Immunological monitoring was obtained with the "multitest CMI", a disposable skin test to evaluate changes of lymphocytes, especially T cells. Results shows a significant increase of response in patients treated with thymostimulin versus control. A larger sample and a deeper immunitary assessment will be provided in the future.

Adjuvants, Immunologic↗
PubMed1993

Noninvasive arterial monitor for quantitative oxygen-15-water blood flow studies.

A noninvasive monitor has been developed for monitoring arterial radioactivity in quantitative PET studies of blood flow. The significance of this probe is that quantitative blood flow studies can be performed without the use of arterial catheterization. The method employed is based on the flux of photons emanating from the superior lobe of the right lung following an intravenous bolus of H2(15)O. Calibration of the monitor is obtained by measuring the relationship between lung monitor counts and arterial radioactivity after arterial and venous radioactivity levels have equilibrated following inhalation of C15O. To determine the accuracy of the lung probe as a measure of arterial radioactivity, 44 brain blood flow determinations were made in 11 volunteers using arterial radioactivity measures based both on the lung probe and continuous sampling from a radial artery. Repeated measures analysis of variance found no differences between invasive and noninvasive estimates of blood flow. These results suggest that the lung monitor enables quantitation of cerebral blood flow yet avoids the trauma of an arterial puncture.

Adult↗
PubMed1992

A dynamic dual isotope radionuclear method of quantifying penile blood flow.

A new radionuclear method of quantifying arterial and venous blood flow of the penis is described. The technique is based on the simultaneous recording of the change in blood volume and venous outflow in the flaccid and erect states, which is produced pharmacologically. The change in penile blood volume is determined by measuring the change in the technetium-labeled red blood cell activity with time. Venous outflow is recorded with a xenon washout technique. The isotope data are used to compute arterial and venous flows with a complex computerized mathematical formula. Three basic blood flow patterns have been noted that distinguish normal patients from those with arterial insufficiency and venous leakage. The study is relatively easy and noninvasive to perform, and it appears to quantify penile blood flow accurately.

Adult↗
PubMed1992

Principles and clinical applications of positron emission tomography.

The basics of positron emission tomography (PET) are presented, including the physics, instrumentation, and radiopharmaceuticals involved; the clinical and research applications; and the cost. In PET, organic molecules labeled with positron-emitting radionuclides are injected or inhaled, and the high-energy photons produced by annihilation events are detected by paired, integrated crystal detectors. A computer uses the lines of origin of these photons to reconstruct a three-dimensional map of a functioning organ system. The positron-emitting radionuclides most often used are carbon 11, oxygen 15, nitrogen 13, fluorine 18, and rubidium 82. PET imaging centers usually consist of a cyclotron facility, a radiochemistry facility, a PET scanner, and computers for image reconstruction. Radiopharmaceuticals used in PET may be divided into blood flow-imaging agents, metabolic imaging agents, and drug receptor-imaging agents. Although PET is still primarily a research tool, it has shown diagnostic potential in neurology, cardiology, and oncology. It has also shown promise as a tool for pharmacologic assessment, as in studies of the effects of the fluorinated quinolones on cerebral blood flow and glucose metabolism. PET may become important in drug development because it yields specific information relatively noninvasively. A single study carries an average break-even price tag of $1500-$2000; rigorous cost-benefit analyses should be conducted before society is asked to subsidize such costs. Positron emission tomography is a frontier technology for which valuable clinical applications are being discovered. Pharmacists can contribute enormously to PET applications and at the same time establish a unique subspecialty for the profession.

Humans↗
PubMed1992

A dual-radioisotope technique for the evaluation of penile blood flow during tumescence.

A technique is described for concomitant study of both arterial and venous penile blood flow during tumescence. Dual-isotope acquisition is started after labeling red cells in vivo with 99mTc. Xenon-133 in saline is then injected into the corpus cavernosum followed with vasoactive drugs to induce an erection. The resulting xenon and technetium time-activity curves are inputs for a one-compartment model. In 14 subjects, the average peak arterial flow rate (PAF) for normal males was calculated as 13.0 +/- 1.28 ml/min (avg +/- s.d.) compared to 16.1 +/- 5.14 and 5.02 +/- 1.78 ml/min for patients with venous leak (VL) or arterial insufficiency (AI), respectively. Peak venous flows (PVF) were 4.25 +/- 1.17, 12.1 +/- 3.75, and 3.78 +/- 1.00 ml/min for normal, VL and AL respectively. Al patients have significantly lower PAF than normal (p = 0.002) or VL patients (p = 0.018), and VL patients had significantly higher PVF than normal (p = 0.012) or Al (p = 0.018). The technique may be helpful in the study of impotence.

Adult↗
PubMed1991

An assessment of cerebral blood flow and metabolism after fleroxacin therapy.

Cerebral blood flow (CBF), glucose (FDG), and oxygen metabolism (OM) were evaluated by positron emission tomography (PET) in 18 healthy volunteers who were randomized to a 72-hour course of either 600 mg/d of fleroxacin or placebo. Such studies attempted to assess potentially serious, yet unexplained, central nervous system adverse effects of the fluorinated quinolone class. Baseline and postplacebo values for CBF (mL/min/100 g) and FDG (mg/min/100 g) were: 53 +/- 6 and 5.7 +/- 1.8; and 49.6 +/- 4.4, and 5.2 +/- 1.2, respectively. Identical values for fleroxacin were: 53.9 +/- 4.8 and 6.3 +/- 1.1; and 54.4 +/- 2.2 and 6.8 +/- 1.5, respectively. The differences between fleroxacin and placebo were not significant. There was also no effect seen in OM between placebo and the active drug. The authors conclude that short-term administration of fleroxacin does not alter CBF, FDG, or OM in healthy volunteers.

Adult↗
PubMed1991

Measurement of human cerebral blood flow with [15O]butanol and positron emission tomography.

Although H2(15)O is widely used for CBF measurement by positron tomography, it underestimates CBF, especially at elevated flow rates. Several tracers, including butanol, overcome this problem, but the short half-life of 15O provides advantages that cause water to remain the tracer of choice. We report the first use and evaluation of 15O-labeled butanol for CBF measurement. Flow measurements made in a similar fashion with water and butanol at 10-min intervals were compared in normal volunteers under resting and hypercapnic conditions. Regional analysis showed good agreement between the tracers at low flows, and significant underestimation of flow by water relative to butanol in regions of elevated flow. The observed relationship between the tracers and the curve-fitted permeability-surface area product for water (133 ml.100 g-1.min-1) follow the known relationship between water and true flow. These observations indicate that [15O]-butanol provided accurate measurements of human regional CBF under conditions of elevated perfusion. We conclude that butanol is a convenient and accurate method for routine CBF determination by positron emission tomography.

Adult↗
PubMed1991

Noninvasive grading of musculoskeletal tumors using PET.

Twenty-five patients with mass lesions involving the musculoskeletal system were studied with positron emission tomography (PET) in order to determine if a relationship exists between histologic grade and tumor uptake of [fluorine-18]2-deoxy-2-fluoro-D-glucose (FDG). There were 6 benign lesions and 19 malignant lesions of various grades. A high correlation (Rho = 0.83) was found between the normalized uptake of tracer and the NCl grade. The high-grade malignancies had significantly greater (p = 0.0091) uptake of FDG than the combination of benign lesions and low-grade malignancies. All lesions with a normalized uptake value of 1.6 or greater were high-grade, while all lesions less than 1.6 represented either benign tumors or low grade malignancies. This strong relationship between FDG uptake and grade among neoplasms from a wide variety of cell types within a single organ system suggests that the technique may be useful in predicting grade even when the cell type is unknown.

Bone Neoplasms↗
PubMed1990

Continuous arterial positron monitor for quantitation in PET imaging.

Quantitative measures of physiologic function with PET require continuous monitoring of arterial positron isotope concentration. A device has been developed that automates this process. This device has advantages over manual sampling techniques with syringes since fewer personnel are required, measurements are less error prone, and more continuous measures of arterial positron concentration are available. A constant flow infusion/withdrawal pump withdraws blood from the radial artery through a catheter connected to 0.5 mm inner diameter teflon tubing. This tubing is wrapped around a 50 mm thick by 50 mm diameter NaI(T1) crystal that is interfaced to a photomultiplier tube (PMT) and encased in a cylindrical lead shield. This crystal detects 511 Kev photons that result from positron annihilation. The device sensitivity is greater than 240 (cts/sec)/(microCi/ml) corresponding to a peak activity of approximately 10,000 cts/sec for a 50 mCi bolus injection in an adult. The system dynamic response has been measured and the true arterial input function is recovered by deconvolution. The system has been used clinically for more than 400 human PET studies and has been a reliable continuous monitor of arterial positron concentration.

Arteries↗
PubMed1989

Monoclonal antibodies and neuroblastoma.

Several antineuroblastoma monoclonal antibodies (MoAbs) have been described and two have been used in radioimmunoimaging and radioimmunotherapy in patients. MoAb 3F8 is a murine IgG3 antibody specific for the ganglioside GD2. Radioiodine-labeled 3F8 has been shown to specifically target human neuroblastoma in patients, and radioimmunoimaging with this agent has provided consistently high uptakes with tumor-to-background ratios of greater than or equal to 10:1. Radioimmunotherapy has been attempted with both MoAb 3F8 and MoAb UJ13A, and although encouraging results have been obtained, dosimetry data and tissue dose response information for these agents is lacking, which impedes the development of such therapy. 124I, a positron emitter, can be used with 3F8 in positron emission tomography (PET) scanning to provide dosimetry information for radioimmunotherapy. The tumor radiation dose response from radiolabeled MoAb also can be followed with PET images with fluorodeoxyglucose (FDG) scanning of neuroblastoma tumors. Results to date indicate that radioimmunoimaging has clinical use in the diagnosis of neuroblastoma and the potential for radioimmunotherapy for this cancer remains high.

Adolescent↗
PubMed1989

Prediction of changing cerebral blood flow by use of the conjunctival oxygen tension/arterial oxygen tension index.

Current methods of assessing cerebral blood flow (CBF) are limited in their ability to provide data at the bedside in a timely, inexpensive, and continuous fashion. Since the palpebral conjunctiva is perfused by branches of the internal carotid artery, perfusion of this tissue may reflect global CBF. Conjunctival oxygen tension (PcjO2), PaO2, PaCO2, and pH were measured in ten healthy subjects during normal ventilation and active hyperventilation. CBF was measured simultaneously using positron emission tomography. CBF decreased from an average of 64.3 +/- 15.1 ml x 100 g-1 x min-1 during baseline measurements to 33.2 +/- 8.4 ml x 100 g-1 x min-1 during hyperventilation. The ratio of PcjO2 to PaO2 (the PcjO2/PaO2 index) decreased from 0.53 +/- 0.07 to 0.35 +/- 0.09 in the same time period. The PcjO2/PaO2 index was significantly correlated with CBF (r = .78, p less than .001). We conclude that the PcjO2/PaO2 index may reflect the reduction in CBF induced by hyperventilation in normal humans, and should be investigated further as a method of assessing CBF in other settings which can result in globally reduced cerebral perfusion.

Adult↗
PubMed1989

Biodistribution and dosimetry of 3F8 neuroblastoma monoclonal antibody.

A method has been developed for quantitating radiolabeled antibody concentrations from images obtained with standard gamma cameras. The method is based on orthogonal projections and accounts both for the effective attenuation of gamma rays and the finite depth dependent resolution of a gamma camera. The method was verified in experimental phantoms and subsequently used in patient studies to quantitate radiolabeled antibody concentrations in neuroblastoma tumors. The in vivo measurements of tumor radioactivity levels were confirmed at biopsy in one patient.

Antibodies, Monoclonal↗